Hair follicle stem cell differentiation is inhibited through a cross talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia

Br J Dermatol. 2012 Jan 27. doi: 10.1111/j.1365-2133.2012.10856.x. [Epub ahead of print]
Hair follicle stem cell differentiation is inhibited through a cross talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia.
Leirós GJ, Attorresi AI, Balañá ME.

Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468 (C1440FFX) -Ciudad de Buenos Aires - Argentina.

Background:  Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/ß-catenin signaling is known to positively affect mammalian hair growth. In androgenetic alopecia (AGA) androgens cause HF miniaturization through a mechanism which remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells. Objectives:  To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells. Methods:  HF stem cell differentiation was evaluated in a co-culture model with DPC or culturing them with media conditioned by DPC after activation of androgen and Wnt/ß-catenin signalling pathways. To study the molecular cross talk between androgen and Wnt signalling pathway in DPC, we analyzed the expression and activation of downstream Wnt signalling molecules in the presence of androgens. Results:  In a co-culture model with human DPC from patients suffering AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 (K6hf) expression. Wnt signaling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and up-regulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition. Conclusions:  These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.

CS - whats the most useful academic article you've found that had practical implications in clinical use? Im not try to to be sarcastic, I'm really just curious. I think it was you whose pointed out that the clinical/practical implications lag far behind the cutting edge science. Anything within the last year that would be useful for our hair protocols?